The aim of the study is to investigate the safety, tolerability, efficacy and pharmacokinetics (PK) for Japanese hepatocellular carcinoma which are not amenable to curative surgery or loco regional therapy

Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]

The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase [ALP] elevation >5x ULN, or total bilirubin >3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP > baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.

Secondary Outcome Measures:

Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]

Objective response (Complete response (CR) + Partial response (PR), regardless of confirmation) is derived from a patient's best objective response by RECIST. Best objective response is calculated based on the "overall" visit response from each assessment. Best objective response represents the best response a patient has had during their time in the study up until progression, last evaluable assessment in the absence of progression or the start of subsequent anti-cancer therapy. For patients whose progression event is death, best objective response will be calculated based on data up until the last evaluable RECIST assessment prior to death.

PFS is defined as the duration from start date of the study treatment to PD according to RECIST 1.0, or any death whichever occurs earlier.

Time to Progression (TTP) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]

TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.

Number of Participants With Response by Alpha Fetoprotein (AFP) [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]

Response by AFP is defined as 20% or more decline in AFP between the baseline value and the AFP value after three courses (12 weeks) of therapy. If patients only receive two courses of therapy the AFP value after two courses (8 weeks) will be used for the analysis.

Written informed consent in accordance with good clinical practice (GCP)

Exclusion criteria:

More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (HCC)

Fibrolamellar HCC

Uncontrolled or refractory ascites

Inadequate organ function

Variceal bleeding within 6 months or the presence of inappropriate varices

History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months

Major surgery within 4 weeks

Known inherited predisposition to bleeding or thrombosis

Significant cardiovascular diseases

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594125